Newly Discovered Cause of Aging in Mammals Possibly Reversible

Researchers have uncovered a cause of aging in mammals that may be reversible.

Published in the journal Cell, the finding had to do with a series of molecular events that allow a cell's nucleus and mitochondria, known as the cell's powerhouse, to communicate. As communication between the two suffers, aging speeds up.

Working with older mice, the scientists found communication could be restored by administering a naturally occurring molecule produced by the human body. Tissue samples taken after treatment exhibited key biological hallmarks similar to those in younger animals.

A cloud of skepticism has long hung over efforts to reverse aging given that common wisdom held that it could be traced back to mutations in mitochondrial DNA, and mutations are irreversible.

David Sinclair, a geneticist from Harvard Medical School and lead author of the study, has worked for years with his team have studied the slow decline of the body, largely focusing on a group of genes known as sirtuins. In the past, they discovered that the compound known as resveratrol - found in grapes, red wine and some nuts - activates a sirtuin gene called SIRT1.

Removing the SIRT1 gene from mice, they found, resulted in signs of aging - including mitochondrial dysfunction. But while this was to be expected, the researchers were surprised to see that most of the mitochondrial proteins coming from the cell's nucleus were at normal levels. Only those the mitochondrial genome encoded were reduced.

Investigating the reason for this revealed a complex series of events triggered by a chemical called NAD and concluded by a key molecule responsible for transporting information and coordinating between the cell's nuclear genome and mitochondrial genome. So long as coordination between the two remained strong, the cells remained healthy.

SIRT1's role in all of this is something like a security guard. It's task is to protect the communication process against a trouble-making molecule known as HIF-1.

As we age, our levels of NAD drop, and SIRT1 becomes less and less able to monitor HIF-1, which then sabotages the cross-genome conversations. After a while, the cell's capacity to produce energy suffers and signs of aging begin to creep in.

"This particular component of the aging process had never before been described," said Ana Gomes, a postdoctoral student in the Sinclair lab.

By administering a compound that cells are able to turn into NAD, Gomes was able to fix the network, restoring communication and mitochondrial function. What's more, if the compound was given before too much mutation accumulation, aspects of the aging process were reversed.

"The aging process we discovered is like a married couple - when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down," Sinclair said. "And just like with a couple, restoring communication solved the problem."